Multidrug resistance-associated polypeptide

Abstract

Compositions and methods are disclosed for improving the effectiveness of a chemotherapeutic regimen to eradicate multidrug-resistant transformed cells from the body of a mammal, preferably from the body of a human. The present disclosure capitalizes on the discovery of a novel multidrug-resistance associated protein (MRP), herein designated MRP-β. The disclosed compositions include MRP-α nucleic acids, including probes and antisense oligonucleotides, MRP-β polypeptides and antibodies, MRP-β expressing host cells, and non-human mammals transgenic or nullizygous for MRP-β. The disclosed methods include methods for attenuating aberrant MRP-β gene expression, protein production and/or protein function. In addition, methods are disclosed for identifying and using a modulator, such as an inhibitor, of MRP-β. Preferably, the modulator is a small molecule.

What is claimed is: 
     
       1. An isolated nucleic acid molecule which encodes an MRP-β polypeptide which functions to transport, expel, or sequester substances from an intracellular milieu, wherein the nucleic acid molecule hybridizes to a nucleic acid molecule having the nucleotide sequence of SEQ ID NO: 1, or a complement thereof, under conditions of hybridization in 0.5M NaHPO 4  at 65° C. followed by washing in 0.1× SSC at 68° C. 
     
     
       2. The isolated nucleic acid molecule of claim 1 comprising the nucleotide sequence of SEQ ID NO: 1 or the complement thereof. 
     
     
       3. The isolated nucleic acid molecule of claim 1 comprising the nucleotide sequence of SEQ ID NO: 1. 
     
     
       4. The isolated nucleic acid molecule of claim 1 consisting of the nucleotide sequence of SEQ ID NO: 1. 
     
     
       5. An expression vector comprising the nucleic acid molecule of any of claims 1 to 4. 
     
     
       6. A cell transfected with the expression vector of claim 5. 
     
     
       7. A cell of claim 6 that is immortalized under cell culture conditions. 
     
     
       8. A cell of claim 6 that is of human origin. 
     
     
       9. A cell of claim 6 that is a unicellular organism. 
     
     
       10. A cell of claim 6 that is a yeast cell.